tbuckley/cabot-search huggingface dataset:
Swiss public health measures associated with reduced SARS-CoV-2 transmission using genome data
Authors: Sarah A. Nadeau, Timothy G. Vaughan, Christiane Beckmann, Ivan Topolsky, Chaoran Chen, Emma Hodcroft, Tobias Schär, Ina Nissen, Natascha Santacroce, Elodie Burcklen, Pedro Ferreira, Kim Philipp Jablonski, Susana Posada-Céspedes, Vincenzo Capece, Sophie Seidel, Noemi Santamaria de Souza, Julia M. Martinez-Gomez, Phil Cheng, Philipp P. Bosshard, Mitchell P. Levesque, Verena Kufner, Stefan Schmutz, Maryam Zaheri, Michael Huber, Alexandra Trkola, Samuel Cordey, Florian Laubscher, Ana Rita Gonçalves, Sébastien Aeby, Trestan Pillonel, Damien Jacot, Claire Bertelli, Gilbert Greub, Karoline Leuzinger, Madlen Stange, Alfredo Mari, Tim Roloff, Helena Seth-Smith, Hans H. Hirsch, Adrian Egli, Maurice Redondo, Olivier Kobel, Christoph Noppen, Louis du Plessis, Niko Beerenwinkel, Richard A. Neher, Christian Beisel, Tanja Stadler
Journal: Science Translational Medicine (2022)

Genome sequences from evolving infectious pathogens allow quantification of case introductions and local transmission dynamics. We sequenced 11,357 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Switzerland in 2020-the sixth largest effort globally. Using a representative subset of these data, we estimated viral introductions to Switzerland and their persistence over the course of 2020. We contrasted these estimates with simple null models representing the absence of certain public health measures. We show that Switzerland's border closures decoupled case introductions from incidence in neighboring countries. Under a simple model, we estimate an 86 to 98% reduction in introductions during Switzerland's strictest border closures. Furthermore, the Swiss 2020 partial lockdown roughly halved the time for sampled introductions to die out. Last, we quantified local transmission dynamics once introductions into Switzerland occurred using a phylodynamic model. We found that transmission slowed 35 to 63% upon outbreak detection in summer 2020 but not in fall. This finding may indicate successful contact tracing over summer before overburdening in fall. The study highlights the added value of genome sequencing data for understanding transmission dynamics.
Combination Therapies with CDK4/6 Inhibitors to Treat <i>KRAS-</i>Mutant Pancreatic Cancer
Authors: Craig M. Goodwin, Andrew M. Waters, Jennifer E. Klomp, Sehrish Javaid, Kirsten L. Bryant, Clint A. Stalnecker, Kristina Drizyte-Miller, Bjoern Papke, Runying Yang, Amber M. Amparo, Irem Ozkan-Dagliyan, Elisa Baldelli, Valerie Calvert, Mariaelena Pierobon, Jessica A. Sorrentino, Andrew P. Beelen, Natalie Bublitz, Mareen Lüthen, Kris C. Wood, Emanuel F. Petricoin, Christine Sers, Autumn J. McRee, Adrienne D. Cox, Channing J. Der
Journal: Cancer Research (2022)

Mutational loss of CDKN2A (encoding p16INK4A) tumor-suppressor function is a key genetic step that complements activation of KRAS in promoting the development and malignant growth of pancreatic ductal adenocarcinoma (PDAC). However, pharmacologic restoration of p16INK4A function with inhibitors of CDK4 and CDK6 (CDK4/6) has shown limited clinical efficacy in PDAC. Here, we found that concurrent treatment with both a CDK4/6 inhibitor (CDK4/6i) and an ERK-MAPK inhibitor (ERKi) synergistically suppresses the growth of PDAC cell lines and organoids by cooperatively blocking CDK4/6i-induced compensatory upregulation of ERK, PI3K, antiapoptotic signaling, and MYC expression. On the basis of these findings, a Phase I clinical trial was initiated to evaluate the ERKi ulixertinib in combination with the CDK4/6i palbociclib in patients with advanced PDAC (NCT03454035). As inhibition of other proteins might also counter CDK4/6i-mediated signaling changes to increase cellular CDK4/6i sensitivity, a CRISPR-Cas9 loss-of-function screen was conducted that revealed a spectrum of functionally diverse genes whose loss enhanced CDK4/6i growth inhibitory activity. These genes were enriched around diverse signaling nodes, including cell-cycle regulatory proteins centered on CDK2 activation, PI3K-AKT-mTOR signaling, SRC family kinases, HDAC proteins, autophagy-activating pathways, chromosome regulation and maintenance, and DNA damage and repair pathways. Novel therapeutic combinations were validated using siRNA and small-molecule inhibitor-based approaches. In addition, genes whose loss imparts a survival advantage were identified (e.g., RB1, PTEN, FBXW7), suggesting possible resistance mechanisms to CDK4/6 inhibition. In summary, this study has identified novel combinations with CDK4/6i that may have clinical benefit to patients with PDAC.
CyclinD2-mediated regulation of neurogenic output from the retinal ciliary margin is perturbed in albinism
Authors: Nefeli Slavi, Revathi Balasubramanian, Melissa Ann Lee, Michael Liapin, Rachel Oaks-Leaf, John Peregrin, Anna Potenski, Carol Marie Troy, Margaret Elizabeth Ross, Eloisa Herrera, Stylianos Kosmidis, Simon William Maxwell John, Carol Ann Mason
Journal: Neuron (2022)

In albinism, aberrations in the ipsi-/contralateral retinal ganglion cell (RGC) ratio compromise the functional integrity of the binocular circuit. Here, we focus on the mouse ciliary margin zone (CMZ), a neurogenic niche at the embryonic peripheral retina, to investigate developmental processes regulating RGC neurogenesis and identity acquisition. We found that the mouse ventral CMZ generates predominantly ipsilaterally projecting RGCs, but this output is altered in the albino visual system because of CyclinD2 downregulation and disturbed timing of the cell cycle. Consequently, albino as well as CyclinD2-deficient pigmented mice exhibit diminished ipsilateral retinogeniculate projection and poor depth perception. In albino mice, pharmacological stimulation of calcium channels, known to upregulate CyclinD2 in other cell types, augmented CyclinD2-dependent neurogenesis of ipsilateral RGCs and improved stereopsis. Together, these results implicate CMZ neurogenesis and its regulators as critical for the formation and function of the mammalian binocular circuit.
Hypoxia-Sensitive COMMD1 Integrates Signaling and Cellular Metabolism in Human Macrophages and Suppresses Osteoclastogenesis
Authors: Koichi Murata, Celestia Fang, Chikashi Terao, Eugenia G. Giannopoulou, Ye Ji Lee, Min Joon Lee, Se-Hwan Mun, Seyeon Bae, Yu Qiao, Ruoxi Yuan, Moritoshi Furu, Hiromu Ito, Koichiro Ohmura, Shuichi Matsuda, Tsuneyo Mimori, Fumihiko Matsuda, Kyung-Hyun Park-Min, Lionel B. Ivashkiv
Journal: Immunity (2022)
Single-cell transcriptome analysis of the in vivo response to viral infection in the cave nectar bat Eonycteris spelaea
Authors: Akshamal M. Gamage, Wharton O.Y. Chan, Feng Zhu, Yan Ting Lim, Sandy Long, Matae Ahn, Chee Wah Tan, Randy Jee Hiang Foo, Wan Rong Sia, Xiao Fang Lim, Haopeng He, Weiwei Zhai, Danielle E. Anderson, Radoslaw Mikolaj Sobota, Charles-Antoine Dutertre, Lin-Fa Wang
Journal: Immunity (2022)
The End
Authors: Jim Johnstone
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Shifting Hepatitis A Epidemiology Requires Renewed Vaccination Efforts
Authors: Bridget M. Kuehn
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Violence against adolescents: prevention must cross the divide between children and women
Authors: Danielle Engel, Seema Vyas, Satvika Chalasani, José Roberto Luna, Alexandra Robinson
Journal: BMJ (2022)

Danielle Engel and colleagues call for an increased focus on adolescents in scaled up programmes for child protection and gender based violence prevention Growing up in a safe and supportive environment is the inherent right of every adolescent and is enshrined in international human rights treaties, including the Convention on the Rights of the Child. It is also essential for their development and wellbeing. The United Nations (UN) H6+ Technical Working Group on Adolescent Health and Wellbeing framework therefore sets out that adolescents need to be physically and psychologically safe and protected from all forms of violence, abuse, and exploitation.1 One billion children experience violence in multiple, often intersecting forms each year (box 1) .6 Gender and age put adolescent girls at a double disadvantage based on intersectional systems of oppression, exclusion, and discrimination.7 Living between childhood and adulthood, their experiences and needs are often overlooked. Interventions, programmes, and policies aimed at tackling violence are generally siloed between protection approaches dealing with violence against children and survivor centred approaches dealing with violence against women. Given the transformational moment embodied in adolescence, to change adolescents' life course for the better by preventing or limiting their exposure to and experience of violence, tackling the specific needs of adolescents is long overdue. Box 1 ### Key terminologyRETURN TO TEXT
Gene Therapy for Sickle Cell Disease, β-Thalassemia Enters Regulatory Reviews
Authors: Howard D. Larkin
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Noninvasive Neuromodulation May Help Improve Function in Cerebral Palsy
Authors: Howard D. Larkin
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Racial and Ethnic Differences in Resident Selection—Reply
Authors: Randall A. Bly, Mark E. Whipple, Sarah N. Bowe
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Quantification of Utilization Management Barriers for Patients Initiating Therapy to Lower Lipid Levels
Authors: Adam O’Neil, Steve Calderbank, James Brown, Joe Vandigo, Perry Yin, Keith Bratti, Scott Howell
Journal: JAMA Network Open (2022)

This cohort study quantifies the rejections that patients with new-to-class claims face when attempting to initiate therapy with PCSK9 inhibitors and explores the association of rejection with subsequent behavior.
Variations in Use of Diabetes Drugs With Cardiovascular Benefits Among Medicaid Patients
Authors: Mike Z. Zhai, Jerry Avorn, Jun Liu, Aaron S. Kesselheim
Journal: JAMA Network Open (2022)

Importance Cardiovascular death remains the leading cause of mortality in patients with type 2 diabetes (T2D). A better understanding of the current use and adoption of glucose-lowering drugs with cardiovascular benefit can inform state policies to ensure their appropriate use in patients with T2D. Objective To characterize the use of glucose-lowering agents with known cardiovascular benefit over time and across states. Design, Setting, and Participants This cross-sectional pharmacoepidemiological study of Medicaid prescription rates of glucose-lowering agents with known cardiovascular benefit vs those with less well-established cardiovascular benefit was conducted between 2014 and 2019. In 50 states and the District of Columbia, the study focused on nonmetformin, noninsulin glucose-lowering drugs divided into 3 cohorts: (1) sodium-glucose cotransporter 2 (SGLT2) inhibitors, (2) glucagon-like peptide 1 (GLP1) receptor agonists, and (3) all other classes of glucose-lowering drugs. Data were analyzed from January 2014 to December 2019. Main Outcomes and Measures Number of days supplied of each cohort, use ratios between the aggregated days supplied of glucose-lowering agents with known cardiovascular benefit vs those with less well-established cardiovascular benefit, and the mean change in use ratios per quarter. Results Across the 50 states and the District of Columbia, the use ratio of glucose-lowering agents with known cardiovascular benefit ranged from 1.58 to 0.14 (mean [SD], 0.48 [0.27]) in 2019. A lower use ratio was seen in states with a higher prevalence of diabetes (β = −0.049; 95% CI, −0.086 to −0.012; P = .01), a larger total population (β = −0.013; 95% CI, −0.023 to −0.003; P = .01), a greater number of Medicaid enrollees (β = −0.054; 95% CI, −0.096 to −0.014; P = .01), a greater proportion of people enrolled in Medicaid (β = −0.018; 95% CI, −0.030 to −0.007; P = .002), and a greater proportion of Medicaid patients enrolled in managed care organizations (β = −0.0032; 95% CI, −0.0051 to −0.0013; P = .002). Higher Medicaid expenditures per enrollee (β = 0.047; 95% CI, 0.007 to 0.089; P = .03) were associated with a higher use ratio of these agents. The relative use of glucose-lowering agents with known cardiovascular benefit by Medicaid enrollees increased 7.4% per year from 2014 to 2019, with wide variations across state Medicaid programs. Conclusions and Relevance In this cross-sectional study, glucose-lowering agents with cardiovascular benefit increased in use during the study period, but also demonstrated considerable variation among states in their relative use. Medicaid programs should try to clarify which factors may be contributing to relative underuse of these potentially life-saving drugs.
Outcomes From Intraoperative Handovers of Anesthesia Care
Authors: Philip M. Jones, Louise Y. Sun, Michael J. Brenner
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Outcomes From Intraoperative Handovers of Anesthesia Care
Authors: Andrea Vannucci, Steven Greenberg, Matthew B. Weinger
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Multi-ancestry meta-analysis of asthma identifies novel associations and highlights the value of increased power and diversity
Authors: Kristin Tsuo, Wei Zhou, Ying Wang, Masahiro Kanai, Shinichi Namba, Rahul Gupta, Lerato Majara, Lethukuthula L. Nkambule, Takayuki Morisaki, Yukinori Okada, Benjamin M. Neale, Mark J. Daly, Alicia R. Martin
Journal: Cell Genomics (2022)

Asthma is a complex disease that varies widely in prevalence across populations. The extent to which genetic variation contributes to these disparities is unclear, as the genetics underlying asthma have been investigated primarily in populations of European descent. As part of the Global Biobank Meta-analysis Initiative, we conducted a large-scale genome-wide association study of asthma (153,763 cases and 1,647,022 controls) via meta-analysis across 22 biobanks spanning multiple ancestries. We discovered 179 asthma-associated loci, 49 of which were not previously reported. Despite the wide range in asthma prevalence among biobanks, we found largely consistent genetic effects across biobanks and ancestries. The meta-analysis also improved polygenic risk prediction in non-European populations compared with previous studies. Additionally, we found considerable genetic overlap between age-of-onset subtypes and between asthma and comorbid diseases. Our work underscores the multi-factorial nature of asthma development and offers insight into its shared genetic architecture.
Trends in Urinary Biomarkers of Exposure to Nicotine and Carcinogens Among Adult e-Cigarette Vapers vs Cigarette Smokers in the US, 2013-2019
Authors: Hongying Daisy Dai, Adam M. Leventhal, Ali S. Khan
Journal: JAMA (2022)

This study assesses temporal trends of biomarkers among adult nicotine and nonnicotine e-cigarette users and cigarette smokers.